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正常化线粒体超氧化物生产阻断了三条高糖损伤的途径
T Nishikawa1, D Edelstein, X L Du
1Albert Einstein College of Medicine, Diabetes Research Centre, Bronx, New York 10461, USA.
Nature
|April 28, 2000
概括
糖尿病高血糖症通过增加线粒体反应性氧物种 (ROS) 来损害血管. 向ROS生产可以防止参与这种高血糖损伤的关键途径.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 糖尿病学 糖尿病学
背景情况:
- 糖尿病高血糖会导致小血管,动脉和外围神经的病态变化.
- 血管内皮细胞是高血糖损伤的主要目标,其潜在机制尚不清楚.
- 这涉及三个关键途径:蛋白激酶C (PKC) 激活,先进的糖化最终产品 (AGEs) 形成,以及阿尔多减少酶途径流动.
研究的目的:
- 研究线粒体活性氧物种 (ROS) 在血管内皮细胞高血糖损伤中的作用.
- 确定线粒体ROS水平的正常化是否可以防止关键生化途径的激活.
主要方法:
- 使用培养的牛大动脉内皮细胞,暴露在高葡萄糖条件下.
- 使用的电子运输链复合体II的抑制剂,氧化酸化的解剂,解蛋白-1和超氧化物解酶.
- 评估了对ROS产生,PKC激活,AGE形成,醇积累和NF-kappaB激活的影响.
主要成果:
- 高血糖症增加了内皮细胞中ROS的产生.
- 针对线粒体ROS生产的抑制剂有效地阻止了这种增加.
- 线粒体ROS水平的正常化取消了葡萄糖诱导的PKC激活,AGE的形成,酸醇的积累和NF-kappaB的激活.
结论:
- 线粒体ROS是血管内皮细胞中高糖损伤的中心调解者.
- 准线粒体ROS生产为糖尿病血管并发症提供了潜在的治疗策略.
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